The objective of this program is to develop new therapeutic options for use in interstitial pulmonary fibrosis (IPF). The central theme of this application involves the study and prevention of the transition from inflammation to fibrosis in the lung. We hope to understand and inhibit the excessive deposition of type I collagen that occurs during fibrogenic processes. Our studies will employ cellular, molecular, and transgenic approaches to study fibrogenesis in vitro, in bleomycin-treated mice, and in fibrogenic lung diseases in humans. The program brings together a group o investigators with long standing interests in inflammation and fibrogenesis and a long tradition 0] interactive science related to pulmonary connective tissue metabolism. The SCOR is composed of 5 interrelated and interacting projects and 3 cores. The Clinical Project 1 will examine the transition of inflammation to fibrosis in patients with IPF and identify markers of lung injury. Project 2 wild examine mechanisms for down-regulating collagen accumulation in the lung, in vitro and in vivo. Project 3 will examine the role of the eosinophil in the pathogenesis of IPF. Project 4 will examine the transcriptional regulation of type 1 collagen by transforming growth factor-beta. Project 5 will examine the function of lysyl oxidase as a pro-inflammatory effector and it's participation in fibrogenesis in vitro and in vivo. Each of these projects combines an exploration into the basic science of the fibrotic process with an effort to test antifibrotic agents in animals or humans. The Administrative Core A will provide managerial support to the program. The Clinical Core B will provide clinical materials, assays, statistical and scientific oversight. The Animal Core C will provide a standardized animal model of fibrosis and will also develop and maintain transgenic animals. The goal of this SCOR Program is to explore new ideas in the pathogenesis and treatment of pulmonary fibrosis. We expect that our approaches will develop new insights and new therapies for pulmonary fibrotic illnesses.